Interferon at the crossroads of SARS-CoV-2 infection and COVID-19 disease

Samuel, Charles E.

doi:10.1016/j.jbc.2023.104960

Cited by 16 publications

(6 citation statements)

References 158 publications

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“…Then, the IFN score declined naturally as in other viral infections. It is now documented that the interferon response and score are only activated during the very early phase of viral infection and will largely be subsided at the end of the first week ( 55 , 56 , 59 ).Therefore our data further confirmed the importance of the timeframe for sample collection and examination of IFN genes Similarly, contradictory results of treatment with various exogenous interferon in different trials could be due to difference in the outcome measures and timing of the interferon administration. Whether interferon is administered early (within the first few days after onset) or late may result in completely different outcomes.…”

Section: Discussionsupporting

confidence: 78%

“…An impaired interferon response had been described by studies that investigated interferon pathway in COVID patients mainly focused on respiratory tissue IFN responses, such as lung tissue ( 54 ) and BALF ( 9 ). However, the ability of the virion to antagonist interferon pathway was only observed in specific in-vitro experiments and the ability of viral proteins to inhibit IFN responses differed among studies ( 55 ). It is not sure to what extent the inhibitory effects were due to overexpression of the viral protein in ectopic subcellular locations ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

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Interferon response and profiling of interferon response genes in peripheral blood of vaccine-naive COVID-19 patients

Huang,

Chiang

et al. 2024

Front. Immunol.

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IntroductionThere is insufficient understanding on systemic interferon (IFN) responses during COVID-19 infection. Early reports indicated that interferon responses were suppressed by the coronavirus (SARS-CoV-2) and clinical trials of administration of various kinds of interferons had been disappointing. Expression of interferon-stimulated genes (ISGs) in peripheral blood (better known as interferon score) has been a well-established bioassay marker of systemic IFN responses in autoimmune diseases. Therefore, with archival samples of a cohort of COVID-19 patients collected before the availability of vaccination, we aimed to better understand this innate immune response by studying the IFN score and related ISGs expression in bulk and single cell RNAs sequencing expression datasets.MethodsIn this study, we recruited 105 patients with COVID-19 and 30 healthy controls in Hong Kong. Clinical risk factors, disease course, and blood sampling times were recovered. Based on a set of five commonly used ISGs (IFIT1, IFIT2, IFI27, SIGLEC1, IFI44L), the IFN score was determined in blood leukocytes collected within 10 days after onset. The analysis was confined to those blood samples collected within 10 days after disease onset. Additional public datasets of bulk gene and single cell RNA sequencing of blood samples were used for the validation of IFN score results.ResultsCompared to the healthy controls, we showed that ISGs expression and IFN score were significantly increased during the first 10 days after COVID infection in majority of patients (71%). Among those low IFN responders, they were more commonly asymptomatic patients (71% vs 25%). 22 patients did not mount an overall significant IFN response and were classified as low IFN responders (IFN score < 1). However, early IFN score or ISGs level was not a prognostic biomarker and could not predict subsequent disease severity. Both IFI27 and SIGLEC1 were monocyte-predominant expressing ISGs and IFI27 were activated even among those low IFN responders as defined by IFN score. In conclusion, a substantial IFN response was documented in this cohort of COVID-19 patients who experience a natural infection before the vaccination era. Like innate immunity towards other virus, the ISGs activation was observed largely during the early course of infection (before day 10). Single-cell RNA sequencing data suggested monocytes were the cell-type that primarily accounted for the activation of two highly responsive ISGs (IFI44L and IFI27).DiscussionAs sampling time and age were two major confounders of ISG expression, they may account for contradicting observations among previous studies. On the other hand, the IFN score was not associated with the severity of the disease.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Interferon response and profiling of interferon response genes in peripheral blood of vaccine-naive COVID-19 patients

Huang,

Chiang

et al. 2024

Front. Immunol.

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“…Свои функции интерфероны I и II типа реализуют путем связывания с трансмембранными рецепторами на клеточной поверхности, что приводит к активации и экспрессии интерферон-стимулируемых генов. Рецепторы к интерферонам I типа, состоящие из двух субъединиц -IFNAR1 и IFNAR2, экспрессируются большинством типов клеток, тогда как рецепторы интерферонов II типа, в частности IFNGR1, -преимущественно клетками иммунной системы [20].…”

Section: новаяunclassified

The impact of polymorphic variants of interferon receptor genes on COVID-19 severity and antibiotic resistance

Krieger,

Samodova,

Svitich

et al. 2024

Russian Journal of Infection and Immunity

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Single nucleotide substitutions in gene sequence associated with conformational changes in protein receptor or in expression of interferon receptors may explain variations in human susceptibility to infection and severity of COVID-19 along with other well-known risk factors. The study aimed to investigate associations between polymorphic variants of interferon receptor genes, COVID-19 severity and prevalence of antibiotic resistance genes in the gut microbiota. Materials and methods. The study was conducted using a random sample of Arkhangelsk population aged 42 to 76 years (n = 305). The research involved gathering COVID-19 data from the Federal Register, conducting blood tests for SARS-CoV-2 antibodies and polymorphic interferon receptor gene variants, and identifying antibiotic resistance genes in stool samples. Results. During the first 12–15 months of the COVID-19 pandemic, 17.4% of the study participants had symptomatic COVID-19, while 32.8% were asymptomatic. By the Autumn of 2022, symptomatic COVID-19 cases rose up to 36.4%, while asymptomatic cases increased to 61.3%. We reveal an association between the CC genotype of the IFNAR1 gene rs2257167 variant, the presence of the T allele of IFNAR2 gene rs2229207 variant, the CCTT haplotype and symptomatic COVID-19. The GCTC haplotype was associated with pneumonia and COVID-19 severity. In November 2022, macrolide resistance genes were observed in 98.4% of cases, whereas those to beta-lactams and glycopeptides — in 26.9% and 13.8% cases, respectively. Resistance to three classes of antibiotics was observed in 4.9% and was more frequently detected in individuals with the ССТТ haplotype. Genes encoding beta-lactamases were more often found in individuals with the GCTC haplotype, those who had COVID-19 with pneumonia and those who received hospital treatment. Glycopeptide resistance genes were associated with the CC genotype of the rs2257167 variant of IFNAR1 gene. Conclusion. We identified genetic determinants of susceptibility, symptomatic infection and COVID-19 severity. The associations between polymorphic variants of interferon receptor genes and COVID-19 severity can be used to identify people with a genetic predisposition to severe infection and to determine priority groups for vaccination, including the prevention of antibiotic resistance in complicated course of viral infections.

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“…Virus-infected cells release small amounts of interferon because gene transcripts cannot leave the nucleus. SARS-CoV-2 is particularly capable of shutting down alarm systems, and infection with this virus releases significantly less interferon than other respiratory viruses, such as SARS-CoV and respiratory syncytial virus [167][168][169][170]. SARS-CoV-2 is a very fast-transmitting virus that has a unique ability to prevent the immune system from recognizing and dealing with it during the early stages of infection [171,172].…”

Section: Rna Genome and Translation In Sars-cov-2mentioning

confidence: 99%

Understanding the Molecular Actions of Spike Glycoprotein in SARS-CoV-2 and Issues of a Novel Therapeutic Strategy for the COVID-19 Vaccine

Matsuzaka,

Yashiro

2024

BioMedInformatics

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In vaccine development, many use the spike protein (S protein), which has multiple “spike-like” structures protruding from the spherical structure of the coronavirus, as an antigen. However, there are concerns about its effectiveness and toxicity. When S protein is used in a vaccine, its ability to attack viruses may be weak, and its effectiveness in eliciting immunity will only last for a short period of time. Moreover, it may cause “antibody-dependent immune enhancement”, which can enhance infections. In addition, the three-dimensional (3D) structure of epitopes is essential for functional analysis and structure-based vaccine design. Additionally, during viral infection, large amounts of extracellular vesicles (EVs) are secreted from infected cells, which function as a communication network between cells and coordinate the response to infection. Under conditions where SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) molecular vaccination produces overwhelming SARS-CoV-2 spike glycoprotein, a significant proportion of the overproduced intracellular spike glycoprotein is transported via EVs. Therefore, it will be important to understand the infection mechanisms of SARA-CoV-2 via EV-dependent and EV-independent uptake into cells and to model the infection processes based on 3D structural features at interaction sites.

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Interferon at the crossroads of SARS-CoV-2 infection and COVID-19 disease

Cited by 16 publications

References 158 publications

Interferon response and profiling of interferon response genes in peripheral blood of vaccine-naive COVID-19 patients

Interferon response and profiling of interferon response genes in peripheral blood of vaccine-naive COVID-19 patients

The impact of polymorphic variants of interferon receptor genes on COVID-19 severity and antibiotic resistance

Understanding the Molecular Actions of Spike Glycoprotein in SARS-CoV-2 and Issues of a Novel Therapeutic Strategy for the COVID-19 Vaccine

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